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Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression
Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073151/ https://www.ncbi.nlm.nih.gov/pubmed/32098246 http://dx.doi.org/10.3390/ijms21041475 |
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author | Cappelletti, Vera Verzoni, Elena Ratta, Raffaele Vismara, Marta Silvestri, Marco Montone, Rosanna Miodini, Patrizia Reduzzi, Carolina Claps, Melanie Sepe, Pierangela Daidone, Maria Grazia Procopio, Giuseppe |
author_facet | Cappelletti, Vera Verzoni, Elena Ratta, Raffaele Vismara, Marta Silvestri, Marco Montone, Rosanna Miodini, Patrizia Reduzzi, Carolina Claps, Melanie Sepe, Pierangela Daidone, Maria Grazia Procopio, Giuseppe |
author_sort | Cappelletti, Vera |
collection | PubMed |
description | Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression. |
format | Online Article Text |
id | pubmed-7073151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70731512020-03-19 Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression Cappelletti, Vera Verzoni, Elena Ratta, Raffaele Vismara, Marta Silvestri, Marco Montone, Rosanna Miodini, Patrizia Reduzzi, Carolina Claps, Melanie Sepe, Pierangela Daidone, Maria Grazia Procopio, Giuseppe Int J Mol Sci Article Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression. MDPI 2020-02-21 /pmc/articles/PMC7073151/ /pubmed/32098246 http://dx.doi.org/10.3390/ijms21041475 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cappelletti, Vera Verzoni, Elena Ratta, Raffaele Vismara, Marta Silvestri, Marco Montone, Rosanna Miodini, Patrizia Reduzzi, Carolina Claps, Melanie Sepe, Pierangela Daidone, Maria Grazia Procopio, Giuseppe Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title | Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title_full | Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title_fullStr | Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title_full_unstemmed | Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title_short | Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression |
title_sort | analysis of single circulating tumor cells in renal cell carcinoma reveals phenotypic heterogeneity and genomic alterations related to progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073151/ https://www.ncbi.nlm.nih.gov/pubmed/32098246 http://dx.doi.org/10.3390/ijms21041475 |
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